Control mechanisms in the regulation of stem cells and tumor cells and their relation to cancer therapy will be studied. Androgens, beta 5-H steroid metabolites, nucleotides, and hyperoxia will be used to alter tumor cell and hematopoietic stem cell cycling to define their use in protection from myelo-suppression and increased sensitivity during chemotherapy and irradiation. Later, when an IND for the steroid metabolite beta5-H-pregnance-beta3-hydroxy-20-one has been procured, clinical observation on the potential use of this compound along with androgenic hormones will be pursued. These objectives will be in the animal models as well as clinical studies. The different stem cell compartments will be evaluated by the method of Till & McCullough (CFU- S), Metcalf (CFU-C) and Stephenson and Axelrod (CFU-E). The effect on the cell cycling will be measured using combinations of CFU enumeration, Fe59 incorporation into RBC and H3 thymidine uptake following interval treatment with chemotherapy, steroids, nucleotides and hyperoxia. For laboratory models both leukemia and solid tumors in different rodent systems will be employed. For the clinical studies, normal male volunteers will serve as controls, and various leukemic, pre-leukemic, and solid tumor patients will be evaluated for the role of the agents previously enumerated during therapy. Preliminary clinical observations relating to possible pyrogenicity of a steroid metabolite are planned. The potential application of the beta5-H steroid metabolites for clinical use in bone marrow depression will be assessed as the different dosage schedules are defined. The synchronization of tumor cells to cycle will be evaluated in increasing susceptibility to cycle specific drugs by the previously mentioned modalities. The effect of exposure to high levels of oxygen will be investigated in both normal and patients undergoing cancer therapy.